Dacomitinib Plus PD-0325901 in Advanced KRAS Mutant NSCLC (M13DAP)

Phase I/II Study With the Combination of Dacomitinib and PD-0325901 in Metastatic KRAS Mutation Positive Non-small Cell Lung Cancer

This is a phase I/II multi-center open-label proof of concept study, consisting of two parts. Part A of this study is designed to identify the recommended phase 2 dose (RP2D) of the combination regimen of dacomitinib plus PD-0325901 in patients with advanced KRAS mutant (KRASm) non-small cell lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the combination of dacomitinib and PD-0325901 versus standard of care therapy in patients with advanced KRASm NSCLC. It is hypothesized that with this combination strategy the progression free survival of patients with KRASm NSCLC will be doubled.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: PD-0325901; Drug: Dacomitinib

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • The Netherlands Cancer Institute
  • Rotterdam, Netherlands, 3015CE
    • Erasmus Medical Center Cancer Institute
  • Utrecht, Netherlands, 3584CX
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological or cytological proof of advanced non-small cell lung cancer
• Written documentation of KRAS (exon 2, 3 or 4) mutation
• At least 18 years of age or older
• Able and willing to give written informed consent
• WHO performance status of 0 or 1

Exclusion Criteria:

• Symptomatic or untreated leptomeningeal disease
• Symptomatic brain metastasis
• Impairment of gastrointestinal function
• Uncontrolled infectious disease
• Left ventricular ejection fraction < 50%
• Retinal degenerative disease or with history of uveitis, retinal vein occlusion or retinal detachment

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dacomitinib + PD-0325901; Dacomitinib: oral tablets PD-0325901: oral capsules	Drug: Docetaxel; Drug: PD-0325901; Drug: Dacomitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence rate of dose-limiting toxicities	1.5 years
Progression free survival	2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 years
Plasma concentration	2.5 years
Time to response	2.5 years
Incidence and severity of adverse events	2.5 years
Overall response rate	2.5 years
Duration of response	1.5 years

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Pfizer
• Investigators: Study Director: f opdam, MD, PhD, The Netherlands Cancer Institute; Principal Investigator: FALM Eskens, PhD, Erasmus Medical Centre Cancer Institute; Principal Investigator: MPJK Lolkema, PhD, UMC Utrecht

Publications and helpful links

General Publications

• van Geel RMJM, van Brummelen EMJ, Eskens FALM, Huijberts SCFA, de Vos FYFL, Lolkema MPJK, Devriese LA, Opdam FL, Marchetti S, Steeghs N, Monkhorst K, Thijssen B, Rosing H, Huitema ADR, Beijnen JH, Bernards R, Schellens JHM. Phase 1 study of the pan-HER inhibitor dacomitinib plus the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutation-positive colorectal, non-small-cell lung and pancreatic cancer. Br J Cancer. 2020 Apr;122(8):1166-1174. doi: 10.1038/s41416-020-0776-z. Epub 2020 Mar 9.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2014
• Primary Completion (Actual): August 7, 2018
• Study Completion (Actual): August 7, 2018

Study Registration Dates

• First Submitted: January 15, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (Estimated): January 17, 2014

Study Record Updates

• Last Update Posted (Actual): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Dacomitinib
• Other Study ID Numbers: NL45985.031.13